Ability to observe cellular processes such as change in morphology, tracking cell fate, and cellular interactions as they happen and documenting them by time-lapse imaging, adds a vital dimension to our understanding of cell function. The advent of fluorescent labeling technologies along with plethora of sophisticated light microscopy techniques and equipments made studying dynamic processes in living cells a common place. However, with many of these instruments, maintaining the health of a cell on a microscope stage for monitoring longer durations is a challenge. The proposed live-cell imaging system (IncucyteTM) is designed to provide continuous, time-lapse images of live cells from within the standard cell-culture carbon dioxide incubator. To the best of our knowledge this is the only instrument that can sit within the standard cell-culture incubator and capable of acquiring both phase contrast and fluorescent images of live cells. The incucyte can hold many different types and brands of standard cell culture vessels ranging from 386-well microplates to T-75 flasks. Users can remotely program the instrument via network accessible GUI to acquire images at different spatial locations and time points. The proprietary HD-phase technology allows taking crispier images with more cell detail and less halo. More importantly, it eliminates fluid-miniscus aberrations that prevent phase contrast imaging in higher format plates such as 96 and 386 well microplates. The incucyte system was extensively tested by several major users for a period of six months using a trial instrument provided by the vendor. With the data generated during the trial period, one of the major users published a paper and the other has a manuscript submitted. The cellular processes and interactions that we anticipate to monitor and image include, but not limited to, epithelial-mesenchymal transitions and tumor-stromal interactions that are critical for tumor metastasis;interactions between T-cell and fibroblast like synoviocytes in Rheumatoid arthritis;fate of mesenchymal stem cells in lung injury and repair;and immune cells and pathogen interactions during host defense.